Priority Research Area Asthma and Allergy

Biochemical Immunology

Projects

Focus of the group Biochemical Immunology is the investigation of cellular interactions of innate immune cells in the regulation of inflammatory and allergic processes. Our research projects are centered on the interplay between mast cells, platelets, and granulocytes and their products, which are investigated on a background of selected clinical pictures on molecular, biochemical, and cellular level. Currently, our group is working on three major projects:

Cellular interactions between mast cells, platelets and granulocytes in the allergic situation

Regulation of inflammatory processes at the interface between vasculature and tissue

Mechanisms of mast cell- and neutrophil-mediated tissue damage in autoimmune diseases of the skin

Allergy

Until now, the role of mast cells in the immune system remains largely elusive and ill defined. Mast cells are able to release a variety of different mediators participating in a wide range of chronic and acute inflammatory diseases. Today it is commonly accepted that investigations limited on these cells alone are not sufficient to understand their impact and physiological function. Therefore, it is necessary to clarify their biological role in dependence on an appropriate cellular context. Until recently, allergic asthma was seen as an eosinophilic inflammation of the airways which was thought to be the reason for the asthmatic dysfunctions of the lung. Today, these events appear to be largely separated and eosinophilia can be overcome without significant changes in the asthma pathology. Within this view, the potential interaction of mast cells and neutrophil granulocytes could be of crucial importance. In a research project of the SFB/Transregio 22 (www.allergie-lunge.de) which is performed in cooperation with the division of Biological Chemistry we are currently investigating the role of mast cells as central regulators of neutrophil recruitment and activation in the allergic lung. Mutual interactions between these cell types could be of key impact for structural and functional changes of the airways during the disease.

Inflammatory processes at the interface between vasculature and tissue

Processes of inflammation are permanently controlled by pro- and anti-inflammatory mechanisms. A significant part of these complex interactions is occupied by different populations of mononuclear phagocytes. Beside dendritic cells, also pro-inflammatory as well as anti-inflammatory (alternative-activated and deactivating) macrophages participate in this regulatory process. Differentiation of these cell populations from blood monocytes requires in addition to direct cell-cell contacts also the presence of several regulatory cytokines. In this project we follow the question, how distinct populations of macrophages with specific regulatory functions are generated in the vasculature. This appears to be from particular physiological relevance, since at least in the beginning of an acute inflammatory process a corresponding cytokine milieu is lacking. According to our hypothesis, the cooperation between defined cytokines released by activated mast cells and the platelet-derived chemokine CXCL4 (platelet factor 4; PF4) initiates the specific programming of monocytes and macrophages.Beside investigations on CXCL4-functions further aims of our group are the analysis of CXCL4-receptors and their corresponding signaling processes in monocytes and T cells (funded by SFB415; http://www.sfb415.uni-kiel.de/de/).

Autoimmunity to type VII collagen

Within the recently established Cluster of Excellence “Inflammation at Interfaces” (www.inflammation-at-interfaces.de) we cooperate with scientists from different groups of the “Integrative Research Network H” on the research on Epidermolysis bullosa acquisita (EBA). This autoimmune disease is characterized by auto-antibodies directed against endogenous type VII collagen leading to a chronic life threatening blistering skin disease. Neutrophils and their products such as proteases and reactive oxygen species have been identified as essential mediators of tissue damage. However, the mechanisms underlying neutrophil activation as well as those that are responsible for the life-long maintenance of the disease, are currently unclear. Comparable to the situation in the chronically inflamed lung, we suggest that activated mast cells initiate the recruitment of neutrophils to the skin. Further interaction of both cell types could lead to a self-amplification of the inflammation which may be responsible for the chronic outcome of the disease.